The candidate of this K01 Mentored Research Scientist Development Award application, Stephanie L. Collins, Ph.D., requests support for a 5-year program of training and research aimed at developing expertise n the development, execution and analysis of human laboratory research studies for substance use disorders. Dr. Collins proposes career development activities that build on her background in preclinical laboratory animal research and capitalize on the resources of Columbia University and the New York State Psychiatric Institute to aid her achieving the long-term goal of becoming an independent investigator. As part of a comprehensive educational plan under the sponsorship of Dr. Suzette M. Evans, and with the guidance from other senior researchers, Dr. Collins will receive intensive mentoring and didactics in biostatistics, human laboratory research study design, the ethical conduct of human research, manuscript preparation and grant writing and management. The proposed research plan consists of studies to examine the role of sex differences and drug use history in impulsivity and stimulant use. Stimulant use is still prevalent nationwide and effective treatment for stimulant dependence remains a challenge. Thus, there is a need for a greater understanding of factors underlying the development of stimulant dependence. Although impulsivity has been shown to influence vulnerability to drug dependence, its influence has not been well characterized. The primary assumption underlying this K award is that useful information about factors, such as impulsivity, that affect stimulant dependence can be collected by comparing non-drug users to cocaine-dependent individuals who are not in treatment. A secondary assumption of this proposal is that sex is a modulating factor in the relationship between impulsivity and drug use. The third assumption is that stimulants modulate impulsivity. Aims 1 -3 will be conducted in men and women, to directly address sex differences and impulsivity. Aim 1 will examine whether impulsivity differs in non-drug using men and women compared to cocaine-dependent men and women not seeking treatment. Aim 2 will examine if oral d-amphetamine administration differentially alters behavioral measures of impulsivity in non-drug using men and women compared to cocaine-dependent men and women. Aim 3 will examine if smoked cocaine administration increases behavioral measures of impulsivity in cocaine abusers. Relevance: The proposed studies will provide a better understanding of the variables that may affect stimulant dependence, which will be helpful in designing more effective behavioral and pharmacological treatment interventions.